Active immunity is brought about through the stimulation of the immune
system to produce antigen-specific humoral (antibody) and cell-mediated
immunity. Active immunity involves the production of memory lymphocytes,
in which immunological protection will last for many years, if not for
a lifetime. This effective, memory-based immunity is established
after every natural primary infection. The nature of vaccines is
to elicit this beneficial long-term immunity without inducing disease.
To accomplish this feat, two types of viral vaccines have been readily
employed: live attenuated and inactivated.

Live
Attenuated Vaccines

Most of the live attenuated vaccines in use today are derived from serial
passage in cultured cells, including human diploid cells (e.g. fetal lung
tissue, other fibroblasts), monkey kidney cells, and chick embryos, among
others. Adaptation of the virus to growth in the cultured cells is
accompanied by a gradual loss of virulence for the natural host.
The neurovirulence of the attenuated virus is tested in mice and primates
before conducting trials with humans. This procedure relies on the
accumulation of point mutations to confer avirulence; however, more exact
mutations can be attained through genetic engineering. Temperature
sensitive mutants, deletion mutants, site-directed mutatgenesis, and live
recombinant viruses are all methods that are commonly employed to achieve
viral attenuation. These vaccines generally possess the following
properties:

derived from wild virus

attenuated through repeated culturing or recombination

must replicate to be effective

produces strong cellular immune response similar to natural infection

severe reactions possible in immunosuppressed vaccinees

can revert to pathogenic form

require only one or two doses

interference from circulating antibody

require refrigeration or lyophilization (freeze-dry)

unstable

Inactivated
Vaccines

Inactivated viruses are also propagated on a cell culture line, but
they are killed with the use of an inactivating agent such as formalin,
B-propiolactone, and ehtylenimines. The overall goal is to destroying
the infectivity of the virus, while maintaining its immunogenicity.
The overall disadvantage is that the use of these "weaker" vaccines necessitates
multiple booster shots. In cases where the inactivated virion can
still produce a febrile response or a local reaction, purified protein
vaccines are used instead. All the nonessential components of the
virion are removed (with the help of ether and detergents), and only the
relevant immunogenic surface proteins are administered, inducing the production
of neutralizing antibodies to specific epitopes. Other procedures
involve cloning the appropriate genes into prokaryotic cells (e.g. bacteria,
yeast), leading to the production of the immunogenic proteins. Characteristics
of inactivated viral vaccines include:

can be whole or fractional virion

grown in culture and inactivated with heat or chemicals (e.g. formalin)

cannot replicate

minimal interference from circulating antibody

require multiple doses

immune response mostly humoral and short-lived

costlier than live attenuated version

may require adjuvant to help stimulate immunity

not as toxic

safer especially if virus is higly virulent

Additives

Once the viruses have been propogated on the cell culture line, they
undergo a purification process involving cell lysis, ultrafiltration, centrifugation,
sucrose density gradients, suspensions, and exclusion gel chromatography
among many extraction procedures. In the case of inactivated vaccines,
formalin (or any other inactivating compound) and an adjuvant (often aluminum
hydroxide) are added. Vaccines tend to contain several additives
including the following::

Suspending fluids of sterile water or saline

Antibiotics such as neomycin to prevent the growth of bacteria

Aluminum salts to initiate antibody responses

Formalin to inactivate viruses and bacteria

Monosodium glutamate as a stabilizer

Egg protein from viruses cultured in embryonated chicken eggs

Sulfites as preservatives

Thimerosal to prevent spoilage

Administration
of Vaccines

Recommendations for the administration of vaccines in the United States
are determined by public health officials associated with health organizations
such as the Immunization Practices Advisory Committee (ACIP), the American
Academy of Family Physicians (AAFP),
the National Vaccine Advisory Committee, and the American Academy of Pediatrics
(AAP). They determine the appropriate
vaccines, ages, doses, and time schedules for immunization based on theoretical
considerations, experimental trials, and clinical experience.
Depending on the formulation, viral vaccines are administered through
three routes:

Oral administration

Subcutaneous injections are administered in the thigh of infants or in
the deltoid area of adults

Intramuscular injections are generally applied to a large muscle group,
either the anterolateral aspect of the upper thigh in infants and the deltoid
muscle of the upper arm for adults.

Side
Effects

The majority of side effects are limited to local reactions at the site
of injection: redness, swelling, or itching. Allergic responses
(anaphylaxis) can range from mild manifestations to more severe complications
such as hives, swelling of the mouth and throat, difficulty breathing,
hypotension, or shock. These infrequent anaphylactic reactions are
due to overactive immunological responses to vaccine components such as
animal protein, antibiotics, preservatives, and stabilizers. Generally,
inactive vaccines are more tolerated than live, attenuated vaccines that
may elicit febrile conditions, particularly in children. Live vaccines
can potentially revert to more virulent forms, leading to the manifestation
of disease on rare occasions; immunosuppressed individuals are not to receive
live, attenuated vaccinations. Largely in response to the reported
cases of vaccine-associated paralytic polio, the National Vaccine Injury
Compensation Program (VICP) was established by the National Childhood Vaccine
Injury Act of 1986. The program requires physicians and other health-care
providers who administer vaccines to maintain permanent immunization records
and to report occurrences of certain adverse events to the U.S. Department
of Health and Human Services. Information regarding reportable side
effects, compensation, and the procedures for filing a claim can be found
on the VICP webpage.

Vaccine
Suppliers

Several pharmaceutical companies are responsible for supplying the currently
licensed vaccines. Among many suppliers, they include: